An important consequence of the changes in gene transcription
and phenotypic stability that occurs during ageing is a decline in
the maintenance of mitochondrial energy metabolism and antioxidant
defences [105]. Ernesto Carafoli and his colleagues have
stressed how mitochondria play a very significant role in the dysregulation
of Ca2þ signalling that occurs in a number of human
diseases [106,107]. Alterations in mitochondrial energy metabolism
coupled to a reduction of oxidant defences that occur during
Vitamin D deficiency may act together to increase ROS formation
and may be one of the universal drivers of age-related diseases. The
way in which Vitamin D deficiency and a concomitant decline in
both Klotho and Nrf2 function contributes to many diseases may be
explained through the ability of these custodial systems to maintain
the stability of the ROS and Ca2þ signalling systems described
earlier.